p53 in signaling checkpoint arrest or apoptosis

https://doi.org/10.1016/S0959-437X(96)90004-0Get rights and content

Abstract

The cell cycle arrest and apoptotic functions of p53 both contribute to the role of this tumour suppressor protein in preventing replication of cells suffering DNA damage. Although the ability of p53 to function as a sequence-specific transcription factor appears to be directly and causally linked to the implementation of an arrest at the G1 stage of the cell cycle, the contribution of transcriptional activation to the apoptotic response is less clear. I seems likely that several p53 activities, both transcriptionally dependent and transcriptionally independent, can play a role in mediating cell death. The requirement for each of these functions appears to depend on the cell type, the cell environment and other genetic alterations already sustained by the cell in which p53 function is activated.

References (68)

  • P. Shaw et al.

    Induction of apoptosis by wild-type p53 In a human colon tumor-derived cell line

  • H. Hermeking et al.

    Mediation of c-myc-Induced apoptosis by p53

    Science

    (1994)
  • S.W. Lowe et al.

    p53 Is required for radiation-Induced apoptosis In mouse thymocytes

    Nature

    (1993)
  • A.R. Clarke et al.

    Thymoeyte apoptosis Induced by p53-dependent and Independent pathways

    Nature

    (1993)
  • A.J. Wagner et al.

    Myc-mediated apoptosis requires wild-type p53 In a manner Independent of cell cycle arrest and the ability of p53 to Induce p21waf1/cip1

    Genes and Dev

    (1994)
  • S.W. Lowe et al.

    Abrogation of oncogene-associated spoptosis allows transformation of p53 deficient cells

  • H. Symonds et al.

    p53-dependent spoptosis suppresses tumor growth and progression In vivo

    Cell

    (1994)
  • H.C. Pan et al.

    Altered cell cycle regulation In the lens of HPV-16 E6 or E7 transgenk: mice: Implications for tumor suppressor gene function In development

    Genes Dev

    (1994)
  • S.D. Morgenbesser et al.

    p53 dependent apoptosis produced by Rb-deficiency In the developing mouse lens

    Nature

    (1994)
  • M.B. Kasten et al.

    A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 Is defective In ataxia-telonglectesla

    Cell

    (1992)
  • D. Lin et al.

    Growth arrest Induced by wild-type p53 protein blocks cells prior to or near the restriction point In late Gt phase

  • A. Di Leonardo et al.

    DNA damage triggers a prolonged p53-dependent G1 arrest and long-term Induction of CIpl In normal human fibroblasts

    Genes Dev

    (1994)
  • S.M. Cross et al.

    A p53-dependent mouse spindle checkpoint

    Science

    (1995)
  • N. Stewart et al.

    Evidence for a second cell cycle block at G2/M by p53

    Oncogene

    (1995)
  • C. Guillouf et al.

    p53 Involvement In control of G2 exit of the cell cycle: role for DNA damage-Induced spoptosls

    Oncogene

    (1995)
  • M.L. Agarwal et al.

    p53 controls both the G2/M and the Gt cell cycle checkpoints and mediates reversible growth arrest In human fibroblasts

  • J.A. Tietenpol et al.

    Sequence-specific transcriptional activation Is essential for growth suppression by p53

  • T. Crook et al.

    Transcriptional activation by p53 correlates with suppression of growth but not transformation

    Cell

    (1994)
  • S. Rowan et al.

    Spedfic loss of spoptotic but not cell cycle arrest funtion In a human tumour derived p53 mutant

    EMBO J

    (1996)
  • T. Hunter

    Breaking the cycle

    Cell

    (1993)
  • D. Lin et al.

    Constitutive expression of B-myb can bypass p53-Induced Waft/Cipl-mediated G(1) arrest

  • J. Brugarolas et al.

    Radiation-Induced cell cycle arrest compromised by p21 deficiency

    Nature

    (1995)
  • C. Deng et al.

    Mice lacking p21CF11WAFI undergo normal development, but are defective In Gt checkpoint control

    Cell

    (1995)
  • O. Zhan et al.

    The godd and myD genes define a novel set of mammalian genes encoding acidic proteins that synergistically suppress cell growth

    Mol Cell Biol

    (1993)
  • Cited by (0)

    View full text